Microcrystalline cellulose, also known as MCC or cellulose gel, is commonly used in the food industry to enhance the properties or attributes of a final food product. For example, it is used as a binder or further processed into colloidal stabilizer in food applications, including in beverages, bakery fillings, frozen desserts, jams, soups and sauces, and the like. It is also widely used as a binder and disintegrant in pharmaceutical tablets, as a suspending agent in liquid pharmaceutical formulations, and as a binder, disintegrant, and processing aid in industrial applications, in household products such as detergent and/or bleach tablets, in agricultural formulations, and in personal care products such as toothpastes and cosmetics.
Microcrystalline cellulose is typically produced by treating a source of cellulose, preferably alpha cellulose in the form of pulp from fibrous plant materials, with a mineral acid, preferably hydrochloric acid (acid hydrolysis). The acid selectively attacks the less ordered regions of the cellulose polymer chain thereby exposing and freeing the crystalline sites which form crystallite aggregates which constitute the microcrystalline cellulose. These are then separated from the reaction mixture, and washed to remove degraded by-products.
The classic process for MCC production is acid hydrolysis of purified cellulose, pioneered by O. A. Battista (U.S. Pat. Nos. 2,978,446; 3,023,104; and 3,146,168). In efforts to reduce the cost while maintaining or improving the quality of MCC, various alternative processes have been proposed. Among these are steam explosion (U.S. Pat. No. 5,769,934; Ha et al.), reactive extrusion (U.S. Pat. No. 6,228,213; Hanna et al.), and reaction in a reactor pressurized with oxygen and/or carbon dioxide gas and operating at 100 to 200° C. (U.S. Pat. No. 5,543,511; Bergfeld et al.).
While it is known in the art that electron beam treatment depolymerizes cellulosic materials, the production of a functional MCC with good tableting performance and good whiteness may be made by electron beam treatment of cellulosic pulps, especially low cost pulps, has not yet been achieved. Industrial scale electron beam accelerators are used for the treatment. There are generally 3 types of industrial scale electron beam machines: the high voltage (>5 MeV); the medium voltage (400 keV to 5 Mev); and the low voltage (80 keV to 300 keV, sometimes up to 500 keV) machines. A description of electron beam machines useful for the treatment of cellulosic pulps is found in “Industrial Radiation Processing with Electron Beams and X-rays”, 1 May 2011-revision 6 by IAEA and International Irradiation Association. Among all the machines, two lower cost systems of handling rolls (pulp rolls) are of particular interest: (1) IBA Industrial's Easy-e-Beam self-shielded 800 kev100 mA system or its modifications; (2) ESI's low energy EB equipment (which might optionally require two-sided or multi-pass treatment due to penetration depth limitations). The electron beam depolymerization can be done with the irradiation dose between 1 MRad to 15 MRad, preferably between 2 MRad to 15 MRad. Although electron beam treatment may be carried in either wet or dry state, it is typically preferable that the treatment be done on dry or substantially dry cellulosic materials.
In order to be employed as a binder in pharmaceutical applications, it is necessary that MCC possess certain properties including a high degree of whiteness and exhibit desirable tablet compaction properties. In order to obtain MCC exhibiting these properties, the starting cellulosic materials for the commercial production of MCC are predominantly dissolving wood pulps (with alpha-cellulose content higher than 92%). Accordingly, it would be desirable to possess a process for producing MCC suitable for use as pharmaceutical binders from lower cost pulps such as paper grade pulps and others having an alpha-cellulose content below that of the dissolving wood pulps currently employed.
In the past, it has been proposed to enhance the whiteness of MCC produced from such lower cost pulps by conducting bleaching at various stages under different conditions. Thus, U.S. Patent Application 2005/0145351 (Schaible et al) proposes a one step process for producing microcrystalline cellulose which simultaneously hydrolyzing, de-polymerizing and bleaching wood pulp by adding an activated oxygen compound under acid conditions. Somewhat similarly, PCT Patent Application WO 2004/011501 (Kopesky et al) discloses a process for microcrystalline cellulose by subjecting pulp to high shear and temperature conditions while reacting with an active oxygen compound (preferably hydrogen peroxide) under acidic conditions. However, it is well known that acidic peroxide will generate substantial amounts of aldehyde, ketone and some carboxyl groups on cellulosic pulp, leading to color reactions and/or potential reactive interactions with pharmaceutical drugs (API) if used in tablets. Further, it is also well known in the art of hydrogen peroxide bleaching of pulps, that acidic peroxide may present safety hazards in commercial operations due to unstable pockets of un-reacted peroxide.
U.S. Pat. No. 6,392,034 (Trusovs) discloses a process to produce MCC comprising treating a cellulose source material with alkali swelling; followed by hydrogen peroxide to reduce viscosity. The solution is filtered to isolate alkali MCC which is then neutralized by treatment with acid.
U.S. Pat. No. 6,228,213 (Hanna et al) discloses a process wherein MCC is produced by acid hydrolysis, neutralized and washed; then bleached with hydrogen peroxide. Somewhat similarly, U.S. Pat. No. 3,954,727 (Toshkov et al) discloses a process wherein acid hydrolyzed MCC is separated from the hydrolysate, washed, alkalized to pH 9 and bleached with hydrogen peroxide. Unfortunately, the MCC produced by such post-isolation bleaching processes has to be subjected to a further washing step in order to avoid having it discolor over a period of time.
Accordingly, it is unexpected that microcrystalline cellulose with desirable long-lasting color and tableting qualities could be prepared by a process in which an oxidant, preferably hydrogen peroxide, is added to a previously acidic microcrystalline cellulose production reaction mixture, after first neutralizing or alkalizing such reaction mixture.